Metabotropni glutamatni receptor 4

Izvor: Wikipedija
Prijeđi na navigaciju Prijeđi na pretragu
edit
Glutamatni receptor, metabotropni 4
Identifikatori
SimboliGRM4; GPRC1D; MGLUR4; mGlu4
Vanjski IDOMIM604100 MGI1351341 HomoloGene20230 IUPHAR: mGlu4 GeneCards: GRM4 Gene
Pregled RNK izražavanja
podaci
Ortolozi
VrstaČovekMiš
Entrez2914268934
EnsemblENSG00000124493ENSMUSG00000063239
UniProtQ14833Q68EF4
RefSeq (mRNA)NM_000841.2NM_001013385.1
RefSeq (protein)NP_000832.1NP_001013403.1
Lokacija (UCSC)Chr 6:
33.99 - 34.12 Mb
Chr 17:
27.56 - 27.65 Mb
PubMed pretraga[1][2]

Metabotropni glutamatni receptor 4 je protein koji je kod ljudi kodiran GRM4 genom.[1][2][3]

Ovaj protein zajedno sa GRM6, GRM7 i GRM8 pripada grupi III familije metabotropnih glutamatnih receptora. Grupa III receptora je vezana za inhibiciju kaskade cikličnog AMP.[3] Aktivacija GRM4 je potencijao terapeutski korisna u tretmanu Parkinsonove bolesti.

Ligandi

[uredi | uredi kod]

Ortosterni

[uredi | uredi kod]
  • LSP1-2111[4], LSP1-3081: agonisti

Pozitivni alosterni modulatori (PAM)

[uredi | uredi kod]
3d model jedinjenja 22a (Hong 2011)
  • Triciklični tiazolopirazolni derivati jedinjenja 22a: EC50 = 9 nM, Emax = 120%[5]
  • ML-128: EC50 = 240 nM, Emax = 182%[6][7]
  • VU-001171: EC50 = 650 nM, Emax = 141%[8]
  • VU-0155041: podtip-selektivni PAM agonist sa robastnom in vivo aktivnošću[9]
  • PHCCC: PAM mGluR4, negativni alosterni modulator mGluR1,[10] direktni agonist mGluR6[11]

Reference

[uredi | uredi kod]
  1. Makoff A, Lelchuk R, Oxer M, Harrington K, Emson P (Dec 1996). „Molecular characterization and localization of human metabotropic glutamate receptor type 4”. Brain Res Mol Brain Res 37 (1-2): 239–48. DOI:10.1016/0169-328X(95)00321-I. PMID 8738157. 
  2. Wu S, Wright RA, Rockey PK, Burgett SG, Arnold JS, Rosteck PR Jr, Johnson BG, Schoepp DD, Belagaje RM (Apr 1998). „Group III human metabotropic glutamate receptors 4, 7 and 8: molecular cloning, functional expression, and comparison of pharmacological properties in RGT cells”. Brain Res Mol Brain Res 53 (1-2): 88–97. DOI:10.1016/S0169-328X(97)00277-5. PMID 9473604. 
  3. 3,0 3,1 „Entrez Gene: GRM4 glutamate receptor, metabotropic 4”. 
  4. Wierońska JM, Stachowicz K, Pałucha-Poniewiera A, Acher F, Brański P, Pilc A (December 2010). „Metabotropic glutamate receptor 4 novel agonist LSP1-2111 with anxiolytic, but not antidepressant-like activity, mediated by serotonergic and GABAergic systems”. Neuropharmacology 59 (7-8): 627–34. DOI:10.1016/j.neuropharm.2010.08.008. PMID 20713068. 
  5. Hong SP, Liu KG, Ma G, et al. (July 2011). „Tricyclic thiazolopyrazole derivatives as metabotropic glutamate receptor 4 positive allosteric modulators”. J. Med. Chem. 54 (14): 5070–81. DOI:10.1021/jm200290z. PMID 21688779. 
  6. Hopkins CR, Niswender CM, Lewis LM, Weaver CD, Lindsley CW. Discovery of a potent, selective and in vivo active mGluR4 positive allosteric modulator. PMID 21433377. 
  7. Engers DW, Niswender CM, Weaver CD, et al. (July 2009). „Synthesis and evaluation of a series of heterobiarylamides that are centrally penetrant metabotropic glutamate receptor 4 (mGluR4) positive allosteric modulators (PAMs)”. J. Med. Chem. 52 (14): 4115–8. DOI:10.1021/jm9005065. PMC 2765192. PMID 19469556. 
  8. Williams R, Niswender CM, Luo Q, Le U, Conn PJ, Lindsley CW (2009). „Positive allosteric modulators of the metabotropic glutamate receptor subtype 4 (mGluR4). Part II: Challenges in hit-to-lead”. Bioorg. Med. Chem. Lett. 19 (3): 962–6. DOI:10.1016/j.bmcl.2008.11.104. PMID 19097893. 
  9. Niswender CM, Johnson KA, Weaver CD, et al. (2008). „Discovery, characterization, and antiparkinsonian effect of novel positive allosteric modulators of metabotropic glutamate receptor 4”. Mol. Pharmacol. 74 (5): 1345–58. DOI:10.1124/mol.108.049551. PMC 2574552. PMID 18664603. 
  10. Watkins JC, Jane DE (2006). „The glutamate story”. British Journal of Pharmacology 147 (Suppl 1): S100–8. DOI:10.1038/sj.bjp.0706444. PMC 1760733. PMID 16402093. 
  11. Beqollari D, Kammermeier PJ (2008). „The mGlu(4) receptor allosteric modulator N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxamide acts as a direct agonist at mGlu(6) receptors”. European Journal of Pharmacology 589 (1-3): 49–52. DOI:10.1016/j.ejphar.2008.06.054. PMID 18593581. 

Literatura

[uredi | uredi kod]

Spoljašnje veze

[uredi | uredi kod]